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Gallstone Disease

• 20 million Americans, or 12% of adults, have gallstones.
• Rising gallstone prevalence is linked to obesity, insulin resistance, and metabolic syndrome.
• Each year, about 1 million new cases are discovered.
• Roughly one third of gallstones cause symptoms.
• 700,000 cholecystectomies are performed annually for gallstone disease treatment.
• Medical expenses for gallstones exceed $6 billion annually; gallstones result in 3,000 deaths per year, about 0.12% of all deaths.
• People with gallstone disease have increased cardiovascular disease, cancer, and overall mortality.

Types of Gallstones

• Gallstones are classified into cholesterol, pigment, and rare stones based on chemical composition.
• Cholesterol stones constitute approximately 75% of gallstones in the USA and Europe.
• Cholesterol stones are mostly cholesterol monohydrate crystals and amorphous calcium bilirubinate precipitates.
• Pure cholesterol stones and mixed stones containing at least 50% cholesterol by weight are the two types of cholesterol stones.
• About 20% of the gallstones are black pigment stones.
• About 4.5% of the gallstones are brown pigment stones.
• About 0.5% of gallstones include calcium carbonate stones and fatty acid-calcium stones.
• Stones are also classified by location: intrahepatic, gallbladder, and bile duct (choledocholithiasis) stones.
• Brown pigment stones are the predominant type in the intrahepatic system.
• The gallbladder mostly contains cholesterol stones, with a small group of black pigment stones.
• Bile duct stones are typically mixed cholesterol stones.

Epidemiology

• Gallstone incidence investigations are less common than prevalence studies due to statistical analyses.
• Prevalence measures existing cases at a time point.
• Incidence measures new cases within a time period, requiring multiple investigations.
• A Danish study reported gallstone incidence over 5 years at 0.3-3.3% for men and 1.4-3.7% for women, varying with age.
• Women showed a higher incidence than men at ages 30 and 40, which declined with increasing age.
• These may show interaction for genetic and environmental factors
• An Italian population study revealed a yearly incidence of 0.5% for gallstones.
• Risk factors include age, female gender, parity, obesity, and hypertriglyceridemia.
• Longitudinal studies identified age and obesity as risk factors.
• Prevalence of gallstones is 5–20% for women aged 20–55 and 25–30% after age 50; men's prevalence rates are about half that of women of the same age.
• US data shows that, 70-80% of detected stones found at US screening or autopsy are cholesterol.
• The prevalence of gallstones is highest in Native American tribes and lowest in Black Americans.
• Asian populations have intermediate risk and first-degree relatives of people with gallstones are 4.5 times more likely to form them.

Risk Factors

• Epidemiologic studies: cholesterol gallstones infrequently occur in childhood/adolescence.
• Cholesterol gallstone occurrence linearly increases with age in both genders, approaching 50% at age 70 in women.
• Older adults are at greater risk for gallstone complications.
• Mortality from surgery is unacceptably high in patients older than 65
• Cholesterol saturation of bile significantly higher in older women in Sweden and Chile than young controls.
• Aging associates with increased cholesterol gallstone formation
  • Increased biliary secretion
  • Intestinal absorption
  • Decreased hepatic synthesis of bile salts
  • Reduced gallbladder contractility
• At all ages, women are twice as likely as men to form cholesterol gallstones.
• Human and animal studies found
  • Estrogen sex hormones increase risk by augmenting hepatic secretion of biliary cholesterol
  • Leads to increased cholesterol saturation of bile

Diet

• High total calories, total cholesterol, saturated fatty acids, refined carbohydrates, proteins, and salt, and low fiber prevalent in populations with cholesterol cholelithiasis.
• The prevalence of cholesterol gallstone disease is significantly higher in North and South American as well as European populations compared to Asian and African populations.
• Several clinical studies found an association between increase of gallstones in China and westernization of Chinese diet.
• Cholesterol lithiasis is now common in japan after the 1970s since adopting western diet.

Pregnancy and Parity

• Pregnancy increases risk for development of biliary sludge and gallstones.
• Significant increase in estrogen levels lead to more lithogenic bile, causing increased hepatic cholesterol secretion and bile supersaturation.
• Impaired gallbladder motility leads to increase in gallbladder volume and bile stasis.
• Increased progestogen also reduce gallbladder motility
• Risk of gallstone formation high in the third trimester, due to sex hormone plasma concentrations increase.
• Probably a risk factor for gallstones, especially in younger women.

Rapid Weight Loss

• Well-known for the formation of cholesterol gallstones.
• 50% obese patients undergoing gastric bypass surgery form biliary sludge/gallstones within 6 months after surgery.
• 25% of patients undergoing strict diet restrictions show gallstones by 6 months.
• 40% patients display symptoms gallstones after 6 months during the same period.
• Include enhanced hepatic secretion of biliary cholesterol, increased gallbladder mucin production during caloric restriction, and impaired gallbladder motility.
• Reduced prevelance of gallstones from 28% to 3% in obese patients on a very-low-calorie diet using UDCA(600 mg/day.)

TPN

• Associated with developments of cholelithiasis
• Cholocystitis
• Formation of sludge after 3 weeks, often forms because of prolonged fasting
• Sphincter Oddi may fail to relax, leading to preferential bile flow into gallbladder.
• 45% adults and 43% of children after 3 to 4 months, due to serious medical issues.
• CCK safe and cost effective, and should be used routinely.

Biliary Sludge

• A crucial intermediate stage in the pathogenesis of both pigment and cholesterol gallstones.
• Facilitates crystalization and agglomeration of solids
• Precipitation of bili
• Conditions = pregnancy, loss weight, spinal chord injuries and long term
• Reversible in most cases

Drugs

• Oral contraceptive steroids
• Conjugated estrogens
• Use of hormone replacement therapy associated with increased for chole...
• Gallstones and use limited to women who received use opposed to the estrogen
• Activating Sreb0-2, and intereferes with synthesis of cholesterol

Lipid Lowering Drugs

• Can prevent gall stone, reduce biliary rate,
• Clofiate reduce concentration and bile salt
• Inhibits and requires investigation
• Act and facilitate stone, may act bile agents, and desaturate and should not be associated with gallstone

Octeroride and Ceftiziaxone

• Analog increases when administered to patients for treatment in octeotide, approximentaly 28%
• Acromegahc, leads to slugish transit
• Ceftriaxone complexs with calcium to form insoluble salts and leads to a slugish biliary

Lipid Abnormalities

• Inversely correlated with level
• Postively association
• Interealted, high to increase and LDL not likely to be risk

Systemic Disease

Obesity and Insulin Resistance

• Risk factor, rising with WW epidemic
• BMI and a strong
• Gallbladder is more toic

Diabetes Mellitus

• Considered at risk from long
• High risk triglyceride

Disease of Ileum

• Risk factor for gallstone formation
• Impaired in Crohn's disease